Abstract
The mechanism underlying orexin-induced contraction was examined in isolated preparations of guinea pig ileum, in relation to cholinergic transmission. Orexin-A caused contraction of ileal strips in a concentration-dependent manner. 1-(2-Methylbenzoxazol-6-yl)-3-[1,5]napthyridin-4-yl-urea hydrochloride (SB-334867-A) antagonized the orexin-A-induced contraction, with no effects on the acetylcholine-induced contraction and twitch contractions. The orexin-A-induced contraction was inhibited by tetrodotoxin and atropine, but not by hexamethonium, an antagonist of vasoactive intestinal peptide and a mixture of 5-hydroxytryptamine receptor antagonists. Orexin-A evoked an outflow of [3H]acetylcholine from the ileal strips preincubated with [3H]choline, in a concentration-dependent manner, and the orexin-A-evoked outflow was inhibited by tetrodotoxin, indicating that the outflow of [3H]acetylcholine originates from the nerve terminals. The orexin-A-evoked outflow of [3H]acetylcholine was antagonized by SB-334867-A. Thus, orexin-A evokes the release of acetylcholine from the enteric cholinergic neurons due to stimulation of the orexin-1 receptors and then causes contractions of guinea pig ileum.
Copyright 2002 Elsevier Science B.V.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / metabolism
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Animals
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Atropine / pharmacology
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Benzoxazoles / pharmacology
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / pharmacology*
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Enteric Nervous System / drug effects
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Female
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Ganglionic Blockers / pharmacology
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Guinea Pigs
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Hexamethonium / pharmacology
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Ileum / drug effects*
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Ileum / innervation
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Ileum / metabolism
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In Vitro Techniques
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Intracellular Signaling Peptides and Proteins*
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Male
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Muscarinic Antagonists / pharmacology
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects*
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Muscle, Smooth / innervation
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Muscle, Smooth / metabolism
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Naphthyridines
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Neurons / physiology*
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Neuropeptides / antagonists & inhibitors
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Neuropeptides / pharmacology*
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Orexin Receptors
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Orexins
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Parasympathetic Nervous System / physiology*
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Receptors, G-Protein-Coupled
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Receptors, Neuropeptide / antagonists & inhibitors
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Receptors, Neuropeptide / drug effects
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Tetrodotoxin / pharmacology
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Urea / analogs & derivatives*
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Urea / pharmacology
Substances
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1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
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Benzoxazoles
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Carrier Proteins
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Ganglionic Blockers
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Intracellular Signaling Peptides and Proteins
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Muscarinic Antagonists
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Naphthyridines
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Neuropeptides
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Orexin Receptors
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Orexins
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Receptors, G-Protein-Coupled
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Receptors, Neuropeptide
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Hexamethonium
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Tetrodotoxin
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Atropine
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Urea
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Acetylcholine